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oai:docta.ucm.es:20.500.14352/1377482026-06-26T00:11:14Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Cejas, Jimena del P. author Cañadas Benito, Olga author Ledesma, A. author Rosa, A.S. author Collada Marugán, Ainhoa author Blanco Rivero, Amaya author Pérez Gil, Jesús author Disalvo, E.A. author Frías, María de los A. author 2026-08-15 Pulmonary surfactant forms surface-active films at the air-liquid interface which are essential for alveolar stability but are highly susceptible to oxidative damage under inflammatory conditions. The reactive species hypochlorous acid (HClO/ClO−), generated by activated neutrophils, is a potent oxidant that may compromise surfactant integrity; however, its molecular and functional impact remains incompletely understood. In this study, the effects of oxidative stress induced by HClO/ClO− on the biophysical and structural properties of a fully native porcine surfactant were investigated using Langmuir balance, captive bubble surfactometry, differential scanning calorimetry, FTIR-ATR spectroscopy, and epifluorescence microscopy. Oxidation induced concentration- and time-dependent inhibition of surfactant adsorption and interfacial film stability. Langmuir balance experiments revealed selective disruption of films containing unsaturated phospholipids or native mixtures, while saturated monolayers remained largely unaffected. FTIR-ATR analysis showed perturbations in lipid headgroup regions and protein secondary structure rearrangements towards β-sheet-rich aggregates, consistent with oxidative unfolding and aggregation. These molecular changes compromise protein-lipid interactions, delaying adsorption and respreading at the air-liquid interface. Epifluorescence microscopy further revealed disruption of lateral lipid organization and altered formation of three-dimensional surfactant reservoirs enriched in disordered components. Functional assays confirmed impaired reduction of surface tension during quasi-static cycling, partially alleviated under dynamic cycling, suggesting exclusion or depuration of oxidized components from the interface. Together, these findings demonstrate that neutrophil-derived oxidants progressively compromise pulmonary surfactant by targeting lipid-protein cooperativity, leading to early interfacial dysfunction followed by structural reorganization. This mechanistic insight advances understanding of oxidative surfactant inactivation and supports the development of antioxidant strategies or oxidant-resistant surfactant formulations as potential therapeutic interventions for inflammatory lung injury. Cejas, J. d. P., Cañadas, Ledesma, Rosa, Collada, Blanco-Rivero, Pérez-Gil, Disalvo, & Frías, M. d. l. A. (2026). Disruption of pulmonary surfactant function under oxidative stress: structural and biophysical insights. Journal of Colloid and Interface Science, 716. https://doi.org/10.1016/J.JCIS.2026.140353 0021-9797 10.1016/j.jcis.2026.140353 https://hdl.handle.net/20.500.14352/137748 1095-7103 https://doi.org/10.1016/J.JCIS.2026.140353 https://www.sciencedirect.com/science/article/pii/S0021979726005308?via%3Dihub=&__cf_chl_tk=Xo_dx7dxOQdkdFOm1Q8vSEXKC.gUvgzipJltPlFc_a0-1782291476-1.0.1.1-pI_yUNf9gMjxlg15DSNVe0ZvVszK0uzHIA1DltghiJQ Disruption of pulmonary surfactant function under oxidative stress: structural and biophysical insights